Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes

Thurik, Florentine F.; Ruiter, Marije Lamain-de; Javadi, Ahmad; Kwee, Anneke; Woortmeijer, Heleen; Page-Christiaens, G. C. M. L.; Franx, Arie; Schoot, C. Ellen van der; Koster, Maria P. H.

doi:10.1002/pd.4940

Cited by 31 publications

(28 citation statements)

References 52 publications

(87 reference statements)

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“…The results of five previous studies that measured cff‐DNA in the first trimester are consistent with the findings of our study in that no association exists between cff‐DNA and subsequent SPTB . Two other studies that focused on the second trimester also reached the same conclusion as our study …”

Section: Discussionsupporting

confidence: 92%

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth

et al. 2019

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Objective To evaluate the association between the fetal fraction of cell‐free DNA at the second trimester and subsequent spontaneous preterm birth. Methods In this retrospective cohort study, data were collected from women with singleton pregnancies who underwent noninvasive prenatal testing at 14 to 25 weeks of gestation. The eligible patients were classified into three groups according to pregnancy outcome: birth at ≥37 weeks of gestation (term group), delivery at <34 weeks of gestation (early spontaneous preterm), and delivery at 34+0 to 36+6 weeks of gestation (late spontaneous preterm). Stepwise linear regression was performed to determine the maternal characteristics associated with the fetal fraction of cell‐free DNA. Logistic regression was used to determine the relationship between the fetal fraction of cell‐free DNA and pregnancy outcomes by adjusting for history of preterm birth. Results A total of 8129 singleton pregnancies met the recruitment criteria. Among them, 7790 (95.83%) were in the term group, 284 (3.49%) were in the late spontaneous preterm group, and 55 (0.68%) were in the early spontaneous preterm group. The fetal fraction of cell‐free DNA was negatively correlated with body mass index, maternal age, nulliparity, and history of spontaneous preterm birth; positively correlated with gestational age; and not correlated with assisted reproduction or surface antigen of hepatitis B virus (HBsAg) positivity. After adjusting for history of preterm birth, a logistic regression analysis demonstrated no statistically significant associations between the fetal fraction of cell‐free DNA and spontaneous preterm birth in any of the preterm groups (<34 weeks, 34+0 to 36+6 weeks, and <37 weeks). Conclusion Our preliminary study found no relationship between the fetal fraction on NIPT at the second trimester and subsequent spontaneous preterm birth.

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Section: Discussionsupporting

confidence: 92%

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth

et al. 2019

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“…These results agree with those of Dugoff et al, who found no significant association with high FF measured on first trimester aneuploidy screening and preterm birth in their prospectively enrolled cohort of more than 2,000 women, 11 and prior studies by Thurik et al and Quezada et al who found no association with absolute levels of fetal cfDNA in the first trimester and subsequent development of spontaneous preterm birth. 9,25 High FF in the first trimester does not appear to have prognostic value for preterm birth prediction.…”

Section: Commentsmentioning

confidence: 84%

High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes

et al. 2019

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Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy. Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.

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“…Two of these studies found associations between maternal parameters and cff-DNA. Thurik et al found an inverse association between cff-DNA and maternal obesity and smoking ( Thurik et al . 2016 ).…”

Section: Cell-free Fetal Dnamentioning

confidence: 99%

Cell-free fetal DNA and spontaneous preterm birth

Boeckel¹,

Davidson²,

Norman³

et al. 2018

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Inflammation is known to play a key role in preterm and term parturition. Cell-free fetal DNA (cff-DNA) is present in the maternal circulation and increases with gestational age and some pregnancy complications (e.g. preterm birth, preeclampsia). Microbial DNA and adult cell-free DNA can be pro-inflammatory through DNA-sensing mechanisms such as Toll-like receptor 9 and the Stimulator of Interferon Genes (STING) pathway. However, the pro-inflammatory properties of cff-DNA, and the possible effects of this on pregnancy and parturition are unknown. Clinical studies have quantified cff-DNA levels in the maternal circulation in women who deliver preterm and women who deliver at term and show an association between preterm labor and higher cff-DNA levels in the 2nd, 3rd trimester and at onset of preterm birth symptoms. Together with potential pro-inflammatory properties of cff-DNA, this rise suggests a potential mechanistic role in the pathogenesis of spontaneous preterm birth. In this review, we discuss the evidence linking cff-DNA to adverse pregnancy outcomes, including preterm birth, obtained from preclinical and clinical studies.

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Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes

Abstract: Adjusted first trimester cfpDNA levels are associated with PIH and GDM but probably not with PE or sPB. © 2016 John Wiley & Sons, Ltd.

Cited by 31 publications

References 52 publications

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth

High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes

Cell-free fetal DNA and spontaneous preterm birth

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